J Am Soc Nephrol. 2006 Jan;17(1):26-30.

Identification of BSPRY as a novel auxiliary protein inhibiting TRPV5 activity.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

van de Graaf, S. F., van der Kemp, A. W., van den Berg, D., van Oorschot, M., Hoenderop, J. G., Bindels, R. J.,
["Cell Physiology, Radboud University Nijmegen Medical Centre, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands."]
Transient receptor potential vallinoid 5 (TRPV5) and TRPV6 are the most Ca2+-selective members of the TRP superfamily and are essential for active Ca2+ (re)absorption in epithelia. However, little is known about intracellular proteins that regulate the activity of these channels. This study identified BSPRY (B-box and SPRY-domain containing protein) as a novel factor involved in the control of TRPV5. The interaction between BSPRY and TRPV5 by GST pull-down and co-immunoprecipitation assays was demonstrated. BSPRY showed co-localization with TRPV5 in mouse kidney. Expression of BSPRY resulted in a significant reduction of the Ca2+ influx in Madin-Darby Canine Kidney cells that stably express TRPV5 without affecting channel cell-surface abundance. Finally, BSPRY expression in kidney was increased in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice, suggesting an inverse regulation by vitamin D3. Together, these results demonstrate the physiologic role of the novel protein BSPRY in the regulation of epithelial Ca2+ transport via negative modulation of TRPV5 activity.
PMID: 16380433External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Inference Prediction 16380433
TRPV6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Yeast two-hybrid Mouse 597-601 Mouse Kidney cDNA library 16380433
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vitro validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Fusion protein-pull down assay Mouse 591-595 E. coli Mouse Full-length Xenopus oocyte lysates 16380433
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Fusion protein-pull down assay Mouse Full-length In vitro translation Mouse Full-length E. coli 16380433
TRPV6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Fusion protein-pull down assay Mouse 597-601 E. coli Mouse Full-length Xenopus oocyte lysates 16380433
TRPV6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Fusion protein-pull down assay Mouse Full-length In vitro translation Mouse Full-length E. coli 16380433
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Co-immunoprecipitation MDCK Mouse Full-length Mouse Full-length 16380433
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Co-immunofluorescence staining Mouse kidney section 16380433
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BSPRY Calcium measurement Inhibition 16380433
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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